Our current understanding of the cellular basis of the immune response is based mainly on a strategy which correlates in vitro lymphocyte function with cell-surface phenotype. This approach has resulted in a clearer picture of the division of labor among lymphocytes engaged in DTH, cytotoxic and proliferative responses to alloantigens and "altered self", helper and suppressive functions and "natural killer" activity. However, there remains a large gap in our understanding of the in vivo cellular mechanisms that govern classical transplantation reactions such as GVH disease and homograft rejection, as well as responses to infectious organisms and tumor immunity. For example, although we have succeeded in separating subclasses of T cells that generate cytotoxic cells from those active in proliferative and DTH responses, it would be rash to speculate as to the importance of either subclass in the in vivo homograft reaction. The major purposes of this project are: (1) to establish the separate roles of these functionally distinct subclasses of T cells (and NK cells) in the in vivo response to allografts, infectious agents and tumors and (2) to manipulate these responses by in vivo elimination or enhancement of the relevant lymphocyte subclasses.